This project has as its objectives, the study of vascular endothelium and its unique features which operate to enable the vascular endothelial surface to be relatively non-thrombogenic in comparison with other types of cells which are components of the vessel wall. In preliminary studies, we have extended the existing concepts which indicate that the endothelial cell functions differently in having diminished reactivity to blood platelets and the adherence of platelet aggregates. In addition, we have studied neoplastic endothelial cells from a mouse hemangioma which do not exhibit the non-thrombogenic featuressof normal endothelium either in-vitro or in-vivo. In preliminary collaborative studies with Dr. Bryan Smith using an immunoassay for the assay of prostacyclin (PGI2), we have found that prostacyclin release was a feature of the endothelium, but not with the fibroblasts, smooth muscle cells or the hemangioma cell. Studies will be performed to delineate the stimuli and mechanisms involved in prostacyclin production and release and how this availability of prostacyclin influences platelet adherence to the endothelial manolayer. We will employ cell fusion techniques to obtain hybrids of the normal endothelial cells and cells, which do not produce prostacyclin and have "thrombogenic" surfaces, in order to determine whether the non-thrombogenic features of the endothelium can be alterad and whether this change results from changes in production of prostacyclin or other inhibitors of platelet reactivity. The proposal offers an opportunity to study the effect of genetic modification of a cell with unique function and characteristics.